Intrauterine infection with the oral anaerobe Fusobacterium nucleatum during pregnancy has been linked to adverse fetal outcomes. In this episode, Yiping Han and colleagues characterize the etiology of F. nucleatum-induced placental inflammation in pregnant mice. Moreover, animals given omega-3 fatty acids prior to infection had reduced placental inflammation, decreased bacterial burden, and improved fetal outcomes. Together, these result support further exploration of omega-3 fatty acid supplementation improving adverse pregnancy outcomes.
Fusobacterium nucleatum is an oral anaerobe prevalent in intrauterine infection associated with a wide spectrum of adverse pregnancy outcomes. We demonstrate here that F. nucleatum triggers placental inflammation through maternal, rather than paternal, TLR4-mediated signaling. Elimination of TLR4 from maternal endothelial cells alleviated placental inflammation and reduced fetal and neonatal death, while elimination of TLR4 in the hematopoietic cells had no effect. The placental inflammatory response followed a spatiotemporal pattern, with NF-κB activation observed first in the maternal endothelial cells and then in the decidual cells surrounding the endothelium, followed by induction of inflammatory cytokines and chemokines. Supplementation of pregnant mice with fish oil as a source of omega-3 fatty acids suppressed placental inflammation, reduced F. nucleatum proliferation in the placenta, and increased fetal and neonatal survival. In vitro analysis illustrates that omega-3 fatty acids inhibit bacterial-induced inflammatory responses from human umbilical cord endothelial cells. Our study therefore reveals a mechanism by which microbial infections affect pregnancy and identifies a prophylactic therapy to protect against intrauterine infections.
Jeewon Garcia-So, Xinwen Zhang, Xiaohua Yang, Mara Roxana Rubinstein, De Yu Mao, Jan Kitajewski, Kang Liu, Yiping W. Han